Resveratrol inhibits VEGF expression in human adult RPE cells and limits the development of proliferative vitreoretinopathy, by attenuating transforming growth factor-β2-induced wound closure and cell migration.
These results indicated that application of the dCas9 targeted to the P2 of MDM2 is a potential therapeutic approach to diseases due to the P2-driven aberrant expression of Mdm2 - such as proliferative vitreoretinopathy.
Subretinal injection of vascular endothelial growth factor (VEGF) and Matrigel induced a late-onset vitreoretinal inflammation that gradually developed into PVR.
Interleukin (IL)-10, IL-12p40, IL-6, monocyte chemotactic protein-1, and vascular endothelial growth factor (VEGF) in the SOF with PVR were significantly higher than in those with RRD or MHRD.
HB-EGF expression in fibroproliferative tissue and its stimulatory effect on glial cell proliferation, chemotaxis, and VEGF secretion suggest that HB-EGF may be a factor mediating glial cell responses during PVR.
The presence of mRNA coding for the cytokines interleukin 1 beta (IL-1 beta), interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF alpha) was investigated in 19 epiretinal membranes obtained from eyes undergoing vitrectomy for the treatment of retinal detachment complicated by proliferative vitreoretinopathy.
Blood from 450 patients with (138 cases) and without (312 controls) post-rhegmatogenous retinal detachment (RD) PVR was genotyped to determine polymorphisms located in the TNFα gene.
The cytokine array also showed that TNF-α levels were normal and that corticosteroid-sensitive pathways were absent in fibrotic NIV, helping explain prior failure of these conventional therapeutic approaches.
Furthermore, our experimental results demonstrated that MDM2T309G in hPRPE cells enhanced vitreous-induced cell proliferation and survival, suggesting that this SNP contributes to the pathogenesis of PVR.
The signaling pathway comprising the PI3Ks, along with a Ser/Thr kinase (AKT), a proto-oncogene product (mouse double minute (MDM)2), and a tumor suppressor protein (p53), plays an essential role in experimental proliferative vitreoretinopathy (PVR), which is a fibrotic blinding eye disorder.
Proliferative vitreoretinopathy vitreous stimulated the production of chemokine (C-C motif) ligand (CCL)2, chemokine (C-X-C motif) ligand (CXCL)8, granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-6, and platelet-derived growth factor (PDGF)-BB by ARPE-19 to significantly (P < 0.05) higher levels than vitreous from the RRD1 and RRD2 groups.
After correction for multiple comparisons, four genes were significantly associated with PVR: SMAD7 (P = 0.004), PIK3CG (P = 0.009), TNF locus (P = 0.0005), and TNFR2 (P = 0.019) In the European sample, replication was observed in SMAD7 (P = 0.047) and the TNF locus (P = 0.044).
The murine double minute (MDM)2 is a critical negative regulator of the p53 tumor suppressor, and MDM2 SNP309G is associated with a higher risk of proliferative vitreoretinopathy (PVR); in addition, the MDM2 T309G created using clustered regularly interspaced short palindromic repeats (CRISPR)/associated endonuclease (Cas)9 enhances normal rabbit vitreous-induced expression of MDM2 and survival of primary human retinal pigment epithelial (hRPE) cells in vitro.
The presence of mRNA coding for HPRT, IL-6, IL-1beta, IL-8, and TNFalpha was investigated in 20 vitreous and subretinal fluid (SRF) samples from patients with PVR by reverse transcriptase polymerase chain reaction (RT-PCR).
The study was conducted to establish a model of PVR by inducing EMT in the human RPE cell line ARPE-19, using TGF-beta and EGF and to establish the contribution of gremlin to EMT.